DESCRIPTION (adapted from the application) The normal human kidney has 300,000 to one million nephrons per kidney. A reduced number of nephrons is correlated with hypertension and chronic renal failure. During renal development, several processes influence the number of nephrons that will form. The applicant's long term objective is to study one of these processes, the commitment of undifferentiated mesenchymal cells to an epithelial cell fate. This process is essential because the nephron is formed from mesenchymally-derived epithelial cells. Very little is known about the origin of these epithelial progenitor cells and there are not markers to identify these cells from other types of cells in the mesenchyme. The objective of this proposal is to separate undifferentiated mesenchymal cells into subfractions using flow cytometry, then to test the ability of these subfractions to differentiate in vitro and in vivo. Additionally, the applicant will use replication-defective retroviruses to determine if a single mesenchymal cell can give rise to more than one type of progeny. The proposed career plan will give the applicant training in research ethics, flow cytometry, and emerging techniques to study cell lineage and renal development. Mt. Sinai Medical Center provides an interactive environment to perform these studies. Notably, there are core facilities for flow cytometry and sequencing, and a growing number of investigators who focus on stem cell and progenitor cells.